P510: THE IMPACT OF POST-REMISSION GRANULOCYTE COLONY-STIMULATING FACTOR USE IN THE PHASE 3 STUDIES OF VENETOCLAX COMBINATION TREATMENTS IN PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA
Authors: C. DiNardo, K. Pratz, P. Panayiotidis, X. Wei, V. Vorobyev, Á. Illés, I. Kim, V. Ivanov, G. Ku, C. L. Miller, M. Zhang, F. Tatsch, J. Potluri, X. Schmidt, C. Recher
Journal: HemaSphere (2022)

Background: In the randomized Phase 3 VIALE-A (NCT02993523) and VIALE-C (NCT03069352) trials, venetoclax (Ven) + azacitidine (Aza) and Ven + low-dose cytarabine (LDAC), respectively, improved outcomes vs low intensity chemotherapy in patients (pts) with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC). Evidence is limited on the use of granulocyte colony-stimulating factor (G-CSF) and impact on outcomes in this pt population. Aims: To explore outcomes in pts with post-remission G-CSF use in the VIALE-A and VIALE-C studies. Methods: In VIALE-A, pts received Ven 400 mg or placebo (PBO) daily plus Aza 75 mg/m2 on d 1−7 (28-d cycles). In VIALE-C, pts received Ven 600 mg or PBO daily plus LDAC 20 mg/m2 on d 1−10 (28-d cycles). G-CSF use was given per institutional practice. Here, pts who achieved a best response of complete remission (CR) or CR with incomplete hematologic recovery (CRi) were analyzed by post-remission G-CSF use. Results: In VIALE-A, 190/286 pts (66%) treated with Ven+Aza and 41/145 (28%) pts treated with PBO+Aza achieved CR/CRi; 93 (49%) and 10 (24%) pts with CR/CRi received G-CSF post-remission (median time to first post-remission G-CSF use [range], 36 d [2−483] and 35 d [4−127]), respectively. In VIALE-C, 69/143 pts (48%) treated with Ven+LDAC and 9/68 (13%) pts treated with PBO+LDAC achieved CR/CRi; 30 (43%) and 2 (22%) received G-CSF post-remission (median time to first post-remission G-CSF use [range], 30 d [2−459] and 229 d [169−289]), respectively. In VIALE-A and VIALE-C, baseline demographics were generally similar in Ven-treated pts regardless of post-remission G-CSF use (Table). In VIALE-A, median duration of response (mDOR) for CR/CRi (95% CI) was not reached (NR; 17.5−NR) and was 12.9 mo (7.9−17.3) in the Ven+Aza+G-CSF and Ven+Aza+non-G-CSF groups, respectively (Table); DOR at 12 mo was 67% and 53%. In VIALE-C, mDOR was 10.8 (4.9−17.8) and 11.8 mo (5.9−NR) in the Ven+LDAC+G-CSF and Ven+LDAC+non-G-CSF groups, respectively; DOR at 12 mo was 45% and 49%. In VIALE-A, median overall survival (mOS [95% CI]) was NR (NR−NR) with Ven+Aza+G-CSF and was 21.1 mo (15.2−NR) with Ven+Aza+non-G-CSF; 12-mo OS rates were 83% and 71%. In VIALE-C, mOS was 20.8 (11.9−NR) with Ven+LDAC+G-CSF and 13.7 mo (10.8−NR) with Ven+LDAC+non-G-CSF; 12-mo OS estimates were 68% and 57%. Among 164 evaluable pts in VIALE-A, measurable residual disease response (MRD<10−3) was achieved by 67, of whom 38 (57%) had post-remission G-CSF. In VIALE-C, MRD<10−3 was achieved by 9 of 64 evaluable pts, of whom 6 (67%) had post-remission G-CSF. In VIALE-A, post-remission Gr ≥3 neutropenia and febrile neutropenia (FN) rates were 33% (n=31) and 39% (n=36) with Ven+Aza+G-CSF, and 29% (n=28) and 20% (n=19) with Ven+Aza+non-G-CSF, respectively. Median durations of post-remission Gr ≥3 neutropenia and FN in VIALE-A were 12.5 d and 8 d (Ven+Aza+G-CSF), and 16 d and 10.5 d (Ven+Aza+non-G-CSF). In VIALE-C, post-remission Gr ≥3 neutropenia and FN rates were 53% (n=16) and 23% (n=7) with Ven+LDAC+G-CSF, and 51% (n=20) and 8% (n=3) with Ven+LDAC+non-G-CSF, respectively. Median durations of post-remission Gr ≥3 neutropenia and FN in VIALE-C were 15 d and 6 d (Ven+LDAC+G-CSF), and 12.5 d and 29 d (Ven+LDAC+non-G-CSF). Image:Summary/Conclusion: In VIALE-A and VIALE-C, G-CSF was frequently used per institutional practice post-remission in responding patients to manage neutropenia. Overall, there was a trend towards shorter durations of Gr ≥3 neutropenia and FN with post-remission G-CSF use, without evidence of negative impact on DOR or OS.